Central venous catheters (CVCs) provide reliable venous access for the administration of intravenous fluids, vasoactive medications, broad-spectrum antibiotics, total parenteral nutrition, and renal replacement therapy. While often necessary for the delivery of life-sustaining therapies, CVCs are associated with an increased risk of bloodstream infection. Bloodstream infections related to CVCs are classified according to the CDC’s National Healthcare Safety Network (NHSN) definition of a central line–associated blood stream infection (CLABSI): a laboratory-confirmed bloodstream infection in a patient with a CVC in place for more than 48 hours before blood culture collection, with no alternative source of bacteremia or fungemia.

The risk of CLABSI is high among ICU patients because of frequent placement of multiple catheters, often under emergent conditions, combined with daily access requirements and prolonged catheter dwell times. ^,, Risk factors for CLABSI can be categorized into patient, provider, and device-related factors ( Table 2 ). Patient-related risks include immunocompromised states such as neutropenia, severe burns, malnutrition, a body mass index (BMI) over 40, receipt of total parenteral nutrition, and prolonged hospitalization before catheter placement. ^,, Provider-related risks entail emergent insertion, breaches in aseptic technique, low nurse-to-patient ratios, delayed catheter removal, and frequent catheter manipulation. ^, Device-related factors include site of insertion, insertion technique, the number of lumens, and the indication for use.

CLABSIs are associated with increased length of stay, higher health care costs, and considerable morbidity and mortality. ^,, In response to the substantial clinical and economic burden of CLABSI, health care institutions and regulatory bodies have prioritized the implementation of standardized, evidence-based prevention strategies. ^, These strategies include the following:

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  Perform hand hygiene immediately before and after inserting, replacing, accessing, or dressing a CVC. Acceptable methods include washing with antiseptic soap or using an alcohol-based hand rub. For hands that are not visibly soiled, alcohol-based formulations are preferred. The use of gloves does not eliminate the need for proper hand hygiene.

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  Use insertion checklists that outline the steps required for optimal CVC insertion using aseptic technique. These checklists should be completed by a trained observer who monitors adherence to sterile practices and is authorized to stop the procedure in the event of a protocol breach.

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  Use a comprehensive catheter insertion cart or kit that contains all components necessary for sterile CVC placement.

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  Cleanse the insertion site with an alcohol chlorhexidine containing a minimum of 2% chlorhexidine gluconate. ^, Allow the site to fully dry before skin puncture to maximize efficacy.

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  Use maximal sterile barrier precautions during CVC insertion including mask, cap, sterile gown, sterile gloves, and a large sterile drape the covers the entire patient.

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  Prefer the subclavian vein for CVC placement in ICU patients, unless contraindicated. Individualize site selection by weighing the risks of infectious and noninfectious complications. For example, while the subclavian site reduces infection risk, it increases the risk of pneumothorax and is generally avoided for hemodialysis catheters because of the potential for central vein stenosis. ^,,, Consider the availability of ultrasound guidance and operator experience when selecting an insertion site.

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  Avoid peripherally inserted central venous catheters (PICCs) as a CLABSI prevention strategy, as the infection risk associated with PICCs in hospitalized patients is comparable to that of other CVCs.

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  Apply chlorhexidine-containing dressings to reduce CLABSI risk. ^,

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  Disinfect catheter hubs and injection ports with an alcoholic chlorhexidine solution before each access.

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  Perform daily chlorhexidine bathing for ICU patients to reduce microbial skin colonization and associated blood stream infections.

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  Assess the necessity of each catheter daily and remove any catheter that is no longer clinically indicated.

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  Maintain appropriate nurse-patient ratios and limit the use of float or traveling nurses in ICUs to support adherence to infection prevention protocols. ^,

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  Do not routinely replace CVCs or arterial catheters.

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  Do not use systemic antibiotic prophylaxis for short-term or tunneled catheter insertion.

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  Consider using antiseptic- or antimicrobial-impregnated CVCs in ICUs with persistently elevated CLABSI rates, despite adherence to standard prevention measures.

In addition to effective prevention strategies, it is essential to provide regular education and training to all ICU staff on the indications for intravascular catheter use, aseptic techniques for insertion and maintenance, and appropriate infection control measures. Fostering a culture of safety and interdisciplinary collaboration centered on commitment to best practices is critical for sustained CLABSI prevention.

VAP is defined as a pneumonia that occurs 48 hours or more after endotracheal intubation. Clinically, pneumonia is diagnosed based on the presence of a new or progressive radiographic infiltrate accompanied by worsening oxygenation and systemic signs of infection such as fever, purulent secretions, and leukocytosis. These criteria are neither sensitive nor specific and often fail to correlate with histopathologic findings at autopsy. ^, The subjective nature of this clinical definition contributes to significant interobserver variability and unreliable administrative diagnostic coding data. ^,

Due in part to limitations in pneumonia surveillance definitions, reported reductions in VAP incidence have not consistently correlated with meaningful improvements in patient outcomes. In response, the CDC developed the ventilator-associated events (VAEs) surveillance definition to facilitate more objective and automated detection of clinically significant events.

VAEs are categorized into ventilator-associated condition (VAC), infection-related ventilator-associated complication (IVAC), and possible/probable ventilator-associated pneumonia (PVAP). A VAC is identified when there is an increase in the daily minimum positive end expiratory pressure of ≥3 cm H ₂ O or an increase in the fraction of inspired oxygen (Fi o ₂ ) of ≥20 points sustained for ≥2 calendar days following ≥2 days of stability or decrease in these parameters. An IVAC is defined as a VAC with concurrent signs of infection (temperature <36°C or >38°C or white blood cell count ≤4000 or ≥12,000 cells/mm ³) and the initiation of antibiotics that continues for ≥4 days. A PVAP requires additional microbiologic evidence of infection in a patient meeting IVAC criteria.

VAEs are frequently attributable to etiologies other than VAP, such as pulmonary edema, atelectasis, and acute respiratory distress syndrome. ^, Consequently, the prevalence of PVAP has been shown to diverge from traditional VAP. Nevertheless, both VAP and VAEs have been independently associated with prolonged mechanical ventilation, increased hospital length of stay, and higher mortality.

A fundamental, and perhaps self-evident, risk factor for VAP and VAEs is prolonged mechanical ventilation. ^, Accordingly, factors that contribute to extended ventilator dependence such as positive fluid balance, use of mandatory modes of ventilation, reintubation, and exposure to sedative agents (eg, benzodiazepines, propofol, and opioids) or neuromuscular blocking agents are associated with increased VAE risk (see Table 2 ). ^,, Conversely, interventions that shorten the duration of mechanical ventilation are associated with a reduced VAE incidence. These include spontaneous awakening trials, spontaneous breathing trials, and conservative fluid management strategies. ^,, A comprehensive review of prevention strategies follows.

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  Avoid intubation and reintubation when clinically safe and feasible. Use high-flow nasal oxygen and noninvasive positive pressure ventilation to prevent intubation in patients with hypoxemic respiratory failure and reduce the risk of reintubation following extubation in critically ill patients.

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  Minimize sedation of mechanically ventilated patients. Employ multimodal analgesia and prioritize sedatives other than benzodiazepines. Perform daily spontaneous awakening trials in patients without contraindications. ^,

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  Assess readiness to extubate daily by performing spontaneous breathing trials. ^,

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  Elevate the head of the bed to 30° to 45° to reduce the risk of aspiration.

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  Provide daily oral care with toothbrushing. Avoid routine use of chlorhexidine because of potential harm and lack of consistent benefit. ^,

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  Initiate early enteral nutrition rather than parenteral nutrition. In patients at high risk for aspiration, use postpyloric feeding over gastric feeding.

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  Stress ulcer prophylaxis may be indicated for prevention of gastrointestinal bleeding, but randomized trials show no benefit in reducing nosocomial pneumonia.

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  Routine monitoring of gastric residual volumes is not recommended.

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  Endotracheal tubes with subglottic secretion drainage may be considered in patients anticipated to require mechanical ventilation for more than 48 to 72 hours.

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  Consider selective oral or digestive decontamination in settings with a low prevalence of antibiotic-resistant organisms.

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  Early tracheostomy may reduce VAP rates, shorten the duration of mechanical ventilation, and decrease ICU length of stay; however, evidence does not consistently demonstrate a mortality benefit.

Preventing VAP and other VAE requires a coordinated, multidisciplinary effort focused on consistent adherence to evidence-based practices, often in the form of prevention bundles . Implementation of prevention bundles has been associated with reductions in VAP rates and, in some studies, improvements in ICU length of stay and mortality. ^, While no single prevention bundle has universal consensus, interventions such as staff education, performance feedback, sedation minimization, head-of-bed elevation, toothbrushing, and daily assessment for extubation are among the most consistently supported strategies. Regular monitoring of bundle compliance and VAE outcomes with transparent reporting to clinical teams and senior hospital leadership cultivates shared accountability, promotes continuous quality improvement, and helps sustain long-term success. Although the task is challenging, examples of successful programs show that sustained improvement is achievable.

Catheter-associated urinary tract infection (CAUTI) is defined as the presence of bacteriuria in a patient who has had an indwelling urinary catheter in place for more than 48 hours, accompanied by signs or symptoms suggestive of a urinary tract infection. According to NHSN surveillance criteria, a CAUTI requires significant bacteriuria (≥10 ⁵ colony forming units [CFU]/mL) with no more than two organisms, along with at least one of the following clinical findings: fever, suprapubic pain, or costovertebral angle tenderness.

Although CAUTIs account for over 40% of all hospital-acquired urinary tract infection (UTIs), they represent up to 95% of UTIs occurring in ICUs. In the United States, approximately 12% to 16% of hospitalized patients will have an indwelling urinary catheter during their admission, and the risk of developing bacteriuria increases by an estimated 3% to 7% with each day the catheter remains in place. An estimated 65% to 70% of CAUTI cases are considered preventable with appropriate catheter use and evidence-based infection prevention strategies.

Prolonged duration of catheterization is the most significant and modifiable risk factor for CAUTI, with the risk of infection increasing incrementally each day the catheter remains in place (see Table 2 ). Additional risk factors include female sex, advanced age, diabetes mellitus, nonclosed drainage systems, and extended hospitalization.

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  Avoid unnecessary catheterization: Before placement, clinicians should consider alternative strategies such as intermittent straight catheterization or external urinary devices.

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  Standardize indications: Institutions should establish clear criteria for appropriate use of indwelling catheters. Accepted indications may include perioperative use for selected surgical procedures, accurate urine output monitoring in ICU patients guiding therapy (eg, fluid resuscitation or vasopressors), management of acute urinary retention, promotion of wound healing in patients with incontinence and open pressure ulcers, and end of life care aligned with patient goals. Notably, ICU admission alone should not justify catheter use without a specific clinical indication.

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  Implement a catheter insertion policy emphasizing aseptic technique: Provide education and periodic competency assessments for health care personnel on catheter insertion, maintenance, and removal.

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  Maintain a closed, drainage system with unobstructed urine flow.

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  Evaluate the necessity of indwelling catheters daily and establish nurse-driven protocols to promptly remove catheters that are no longer indicated. ^,

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  Routine use of antimicrobial- or antiseptic-impregnated catheters is not recommended.

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  Do not screen for or treat asymptomatic bacteriuria except in the few patient populations where benefits may exceed harms (eg, pregnant patients and patients undergoing urologic procedures associated with mucosal trauma).

Despite the success of collaborative, multidisciplinary efforts in reducing CAUTI rates on medical-surgical floors, similar progress in the ICU has been more limited. This may stem from the assumption that critical illness justifies prolonged indwelling urinary catheter use, as well as the common practice of pan-culturing in response to fever which often includes unnecessary urine cultures. These patterns underscore the potential harm of urinary catheterization in critically ill patients, including impaired mobility, urethral trauma, heightened delirium risk, asymptomatic bacteriuria leading to inappropriate antibiotic use, and ultimately CAUTI. Given these risks, timely removal of the catheter should be a priority once the original indication has resolved. In many cases, catheter removal is not only a step toward reducing infection risk, but also a meaningful milestone on the path to ICU recovery.

Clostridioides difficile infection (CDI) is defined by presence of clinically significant diarrhea or toxic megacolon without other cause and either a stool test positive for C difficile toxins or toxin-producing C difficile organism or findings of pseudomembranous colitis on colonoscopy or histopathology. Nosocomial diarrhea is a common complication of hospitalized patients, and although CDI is a frequent focus, less than 20% of cases are attributable to CDI. Nevertheless, CDI is associated with approximately half a million infections and roughly 30,000 deaths annually in the United States. ^, In part because of greater emphasis on infection prevention measures, the incidence of health care–associated CDI has declined substantially over the last decade.

The most important modifiable risk factor for CDI is antibiotic exposure (see Table 2 ). Almost all antibiotics have been associated with CDI; however certain classes including third-/fourth-generation cephalosporins, fluroquinolones, carbapenems, and clindamycin are most implicated. Advanced age and prolonged duration of hospitalization are additional, important risk factors. Gastric acid suppression, particularly use of proton pump inhibitors, has been associated with increased risk of CDI; however, restriction of gastric acid suppression has not been established as an effective CDI prevention measure. ^,

Prevention of CDI focuses on the following 2 methods: (1) protecting patients from initial C difficile acquisition and (2) limiting pathogen transmission between patients with CDI and health care practitioners and other patients. Because antibiotic exposure contributes to disruption of the intestinal microbiota and subsequent development of C difficile , avoiding unnecessary antimicrobial use through implementation of an antimicrobial stewardship program is an important measure to curtail initial C difficile acquisition. Large meta-analyses suggest that restrictive antimicrobial stewardship programs, particularly when paired with infection prevention measures, can reduce CDI incidence by 30% to 50%. ^, Additional prevention measures focusing on curtailing spread once a patient has been found to have CDI are as follows.

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  Place patients with CDI on contact precautions, preferably in a single-patient room to help reduce patient-to-patient spread of the organism. Contact precautions should be continued for at least 48 hours after diarrhea has resolved.

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  Providers should don gown and gloves upon entry to the patient’s room, and these should be removed before exiting the room.

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  Perform hand hygiene immediately before donning and after removing PPE. Using soap and water is preferred over alcohol-based hand hygiene, particularly during CDI outbreaks. ^,

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  Use disposable patient equipment (ie, stethoscope) when possible and ensure reusable equipment is thoroughly cleaned and disinfected, preferentially with a sporicidal disinfectant.

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  Conduct terminal ICU room cleaning with a sporicidal agent and incorporate measures of cleaning effectiveness to ensure quality of environmental cleaning.

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  Consider oral vancomycin prophylaxis in patients with a history of CDI who require systemic antibiotics and are at high risk for recurrence. ^,

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  Probiotics are not recommended for routine primary or secondary CDI prophylaxis.

Prevention of CDI in the ICU relies on a close working relationship between ICU health care personnel and the infection prevention team. Integrating and measuring best practices that focus on antimicrobial stewardship, hand hygiene, adherence to contact precautions, and effective environmental cleaning can help prevent the spread of C difficile and ensure the ICU remains a safe environment for patients.

Adherence to the above principles provides a strong foundation for preventing most HAIs; however, critical care physicians must remain adaptable to emerging and uncommon pathogens, as exemplified by the SARS-CoV-2 pandemic. In such scenarios, identify, isolate, and inform paradigm remains essential. Prompt recognition of patients with concerning clinical symptoms, timely isolation with appropriate PPE, and immediate notification of infection prevention teams are critical steps to limiting nosocomial transmission. These same principles underpin efforts to prevent and control outbreaks of MDROs, which represent an ongoing and increasingly complex challenge in the ICU.

MDROs are defined as pathogens resistant to one or more classes of antimicrobial agents. In the ICU, clinicians frequently encounter such organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa (PsA) , carbapenem-resistant Enterobacteriaceae , and Candida auris ( Table 3 ). According to the CDC, HAIs caused by MDROs increased approximately 20% during the COVID-19 pandemic compared to the prepandemic period.

Infections with MDROs are linked to worse clinical outcomes including increased mortality, prolonged length of stay, and higher costs. ^, Risk factors for MDRO acquisition in the ICU include prolonged critical illness, exposure to broad spectrum antibiotics, mechanical ventilation, higher severity of illness, and recent surgical or invasive procedure (see Table 3 ). Moreover, the ICU environment exerts multiple stressors on the patient’s microbiome such as disruption of the gastrointestinal tract, artificial nutrition, antibiotic exposure, and dysglycemia, which collectively diminish microbial diversity, facilitating colonization by resistant organisms. As colonization with MDROs increases, so too does the risk of transmission, most commonly via the hands of health care personnel or through contact with contaminated equipment and surfaces in the patient care environment. Effective infection prevention and control strategies are therefore essential to interrupt transmission and mitigate the impact of MDROs in the ICU.

Prevention of MDRO transmission in the ICU involves both horizontal and vertical strategies. Horizontal strategies are non–pathogen-specific aimed at reducing the overall risk of transmission. These include hand-hygiene, environmental cleaning, universal decolonization (eg, chlorhexidine gluconate bathing), and antimicrobial stewardship. In contrast, vertical strategies are pathogen-specific and focus on identifying and managing carriers of MDROs through active surveillance and targeted interventions such as decolonization protocols or implementation of contact precautions.

Although the incidence of MRSA infections in the United States has declined since the early 2000s, MRSA remains one of the most prevalent health care–associated pathogens in the ICU. In addition, it carries a substantial mortality burden, with one US study reporting an unadjusted in-hospital mortality rate of 29% for hospital-onset MRSA bloodstream infections from 2012 to 2017. Current guidelines recommend that acute care hospitals implement MRSA surveillance programs to evaluate the effectiveness of infection control measures and track hospital-onset cases to assess transmission risk. Among the strategies shown to reduce MRSA transmission and infection in the ICU, universal decolonization, using daily chlorhexidine bathing and intranasal mupirocin for all ICU patients, has demonstrated the most consistent benefit. Although current guidelines continue to recommend contact precautions for patients colonized or infected with MRSA, this practice has been the subject of debate. A recent systematic review article found no significant difference in hospital-associated MRSA infection rates after discontinuing contact precautions.

Enterococci are commensal organisms of the human gastrointestinal tract that can cause invasive infections, particularly in critically ill patients. A meta-analysis reported that 8.8% of patients are colonized with VRE upon ICU admission. This finding becomes clinically significant when considering that 8% of colonized patients may develop an invasive infection within 30 days. In a large ICU point prevalence study, VRE infections were independently associated with increased mortality compared to infections with other microorganisms.

Risk factors for VRE colonization include exposure to antibiotics (particularly vancomycin, third-generation cephalosporins, and metronidazole), prolonged hospitalization, immunosuppression, severe comorbidities, and previous enterococcal infection. ^, VRE is frequently shed in feces and can colonize the skin and contaminate surrounding patient care surfaces. Its hardy nature on environmental fixtures was highlighted by an observational study that identified VRE as the most frequently recovered MDRO, detected in 19% of routine and terminally cleaned patient rooms.

Effective strategies to prevent VRE transmission in the ICU primarily rely on horizontal approaches, including strict hand hygiene adherence and comprehensive environmental cleaning. ^, As with MRSA, the role of contact precautions is controversial. Although historically recommended for VRE, more recent studies suggest that discontinuing contact precautions does not lead to increased rates of hospital-acquired VRE. ^,

PsA is a nonfermenting gram-negative rod that is ubiquitous in the environment and commonly acts as an opportunistic pathogen in critically ill patients with impaired host defenses. A well-known cause of HAIs, PsA ranked as the fifth most common overall HAI pathogen, the second most common cause of VAP, and the third most common cause of CAUTI based on NHSN data from 2018 to 2021. During this period, an average of 11.9% of PsA HAI isolates were MDR. However, in 2020, coinciding with the onset of the COVID-19 pandemic, MDR rates increased by 32% and have remained elevated compared to prepandemic levels.

Mechanisms of antibiotic resistance in MDR PsA are often multifactorial and include the production of ambler class C (AmpC) and extended-spectrum beta-lactamases, overexpression of efflux pumps, porin mutations, and biofilm formation. Its capacity to rapidly acquire chromosomal mutations further contributes to resistance, underscoring the importance of antimicrobial stewardship in minimizing the selective pressure that drives resistance. PsA is frequently found in water sources, including hospital sinks and plumbing, which then serve as persistent environmental reservoirs in ICUs. Notably, several ICU outbreaks of MDR Pseudomonas have been stymied only after identifying and addressing a contaminated water source for PsA. ^,